OFF Pathways Research Articles

Retinal Ganglion Cell Subtypes and Their Vulnerability in Glaucoma.

The detection of selective retinal ganglion cell damage in glaucoma has been a long sought-after goal, not just for the development of clinical tests for the early detection of glaucoma but for the elucidation of potential mechanisms underlying retinal ganglion cell loss. Early reports of the selective vulnerability of larger retinal ganglion cells (RGCs) in human studies did not translate simply to the loss of a particular class of RGC but more likely reflected shrinkage and degeneration across all RGC classes. Subsequent studies of nonhuman primate (NHP) models of glaucoma indicated some selectivity with great damage to the magnocellular vs parvocellular pathways. More recently, rodent models of experimental glaucoma have highlighted a selective vulnerability of OFF-centered RGCs-particularly those with transient responses. Selectivity for OFF pathway damage is also seen as a trend in a rat model of glaucoma. These data support the concept that some RGCs are more vulnerable to the effects of glaucoma damage. This chapter covers some of the methods to elucidate RGC damage and the relevance of model selection to mimic human glaucoma rather than just RGC death.

Understanding contrast perception in amblyopia: a psychophysical analysis of the ON and OFF visual pathways

PurposeThe study aimed to explore potential discrepancies in contrast sensitivity in the ON and OFF visual pathways among individuals with amblyopia compared to controls.MethodsEleven adult amblyopes (26.2 ± 4.4 [SD] years old) and 10 controls (24.6 ± 0.8 years old) with normal or corrected to normal visual acuity (logMAR VA ≤ 0) participated in this study. Using the quick contrast sensitivity function (qCSF) algorithm, we measured balanced CSF which would stimulate the ON and OFF pathways unselectively, and CSFs for increments and decrements that would selectively stimulate the ON and OFF visual pathways. Contrast sensitivity and area under log contrast sensitivity function were extracted for statistical analysis.ResultsFor the balanced CSF, we found significant interocular differences in sensitivity and area under log contrast sensitivity function in both amblyopes [F(1,10) = 74.992, p < 0.001] and controls [F(1,9) = 35.6, p < 0.001], while such differences were more pronounced in amblyopes than in controls. For increment and decrement CSFs, we found that the increment sensitivity (p = 0.038) and area under log contrast sensitivity function (p = 0.001) were significantly lower than the decrement in the amblyopic eye. Such differences between increment and decrement CSFs were not observed in the fellow eye of the amblyopes or in the controls.ConclusionThere is a subtle difference in the contrast sensitivity of the amblyopic eye when exposed to stimulation in the ON and OFF pathways.

The relationship between ON-OFF function and OCT structural and angiographic parameters in early diabetic retinal disease.

This study measured associations between ON and OFF functional indicators and structural optical coherence tomography (OCT) and OCT angiography (OCTA) markers in diabetic retinal disease. Fifty-four participants with type 1 or type 2 diabetes (mean age = 34.1 years; range 18-60) and 48 age-matched controls (mean age = 35.4 years, range 18-59) underwent visual psychophysical testing, OCT and OCTA retinal imaging. Psychophysical tasks measuring (A) contrast increment and decrement sensitivity and (B) response times to increment and decrement targets were assessed as surrogate measures of ON and OFF retinal ganglion cell function. The group with diabetes had worse foveal contrast increment and decrement thresholds (p = 0.04) and were slower to search for increment and decrement targets relative to controls (p = 0.009). Individuals with diabetes had a less circular foveal avascular zone (FAZ) (p < 0.001) but did not differ from controls in foveal vessel density and FAZ area. Functional and structural outcome measures related to the peripheral retina were also comparable between those with and without diabetes. Functional responses to increments and decrements were not significantly correlated with FAZ circularity or vessel density in individuals with diabetes. Diabetic retinal disease results in impaired performance on measures of inferred ON and OFF pathway function in addition to vascular deficits measurable with OCTA. Future longitudinal studies may determine the temporal relationship between these deficits, and whether they predict future diabetic retinopathy.

Investigating ON and OFF pathway spatial tuning in the upper and lower visual fields using the SSVEP

Investigating ON and OFF pathway spatial tuning in the upper and lower visual fields using the SSVEP

Asymmetric Activation of ON and OFF Pathways in the Degenerated Retina.

Retinal prosthetics are one of the leading therapeutic strategies to restore lost vision in patients with retinitis pigmentosa and age-related macular degeneration. Much work has described patterns of spiking in retinal ganglion cells (RGCs) in response to electrical stimulation, but less work has examined the underlying retinal circuitry that is activated by electrical stimulation to drive these responses. Surprisingly, little is known about the role of inhibition in generating electrical responses or how inhibition might be altered during degeneration. Using whole-cell voltage-clamp recordings during subretinal electrical stimulation in the rd10 and wild-type (wt) retina, we found electrically evoked synaptic inputs differed between ON and OFF RGC populations, with ON cells receiving mostly excitation and OFF cells receiving mostly inhibition and very little excitation. We found that the inhibition of OFF bipolar cells limits excitation in OFF RGCs, and a majority of both pre- and postsynaptic inhibition in the OFF pathway arises from glycinergic amacrine cells, and the stimulation of the ON pathway contributes to inhibitory inputs to the RGC. We also show that this presynaptic inhibition in the OFF pathway is greater in the rd10 retina, compared with that in the wt retina.

Invited Session II: Retinal remodeling and regeneration: Partial cone loss triggers differential modification of inhibition across retinal pathways.

Cone loss up to 40-60% can be undetected by visual acuity or sensitivity metrics. These findings suggest that conventional diagnostics can be insensitive to cone loss below a threshold and/or that visual circuits can be resilient to cone loss up to a threshold. To distinguish between these possibilities, our lab studied the effects of partial cone loss in the mature mouse retina. We induced controlled cone loss by selectively expressing the diphtheria toxin receptor under the cone opsin promoter (cone-DTR). We examined the effects of 50% cone loss on the three of the most sensitive cell types in mouse retina: alpha ON sustained (AON-S), OFF sustained (AOFF-S), and OFF transient (AOFF-T) ganglion cells. With multiple cell types, we can discern between effects common across pathways, i.e., changes to common circuit components, and effects unique to pathways, i.e., changes to circuit components after the pathways diverge to each cell type. In AON-S ganglion cells, partial cone loss triggers inhibition to increase spatiotemporal integration, recover contrast gain, and receive increased synaptic inputs. While OFF pathways also exhibit modified spatiotemporal processing with fewer cones, the extent of functional adjustments was unique between the AOFF-S and AOFF-T. Cone loss caused differential modifications to inhibition in each of these retinal pathways. These findings demonstrate that partial cone loss induced circuitry changes after the divergence of OFF retinal pathways.

Contrast Sensitivity of ON and OFF Human Retinal Pathways in Myopia.

The human visual cortex processes light and dark stimuli with ON and OFF pathways that are differently modulated by luminance contrast. We have previously demonstrated that ON cortical pathways have higher contrast sensitivity than OFF cortical pathways and the difference increases with luminance range (defined as the maximum minus minimum luminance in the scene). Here, we demonstrate that these ON-OFF cortical differences are already present in the human retina and that retinal responses measured with electroretinography are more affected by reductions in luminance range than cortical responses measured with electroencephalography. Moreover, we show that ON-OFF pathway differences measured with electroretinography become more pronounced in myopia, a visual disorder that elongates the eye and blurs vision at far distance. We find that, as the eye axial length increases across subjects, ON retinal pathways become less responsive, slower in response latency, less sensitive, and less effective and slower at driving pupil constriction. Based on these results, we conclude that myopia is associated with a deficit in ON pathway function that decreases the ability of the retina to process low contrast and regulate retinal illuminance in bright environments.

A Robust Visual System for Looming Cue Detection Against Translating Motion.

Collision detection is critical for autonomous vehicles or robots to serve human society safely. Detecting looming objects robustly and timely plays an important role in collision avoidance systems. The locust lobula giant movement detector (LGMD1) is specifically selective to looming objects which are on a direct collision course. However, the existing LGMD1 models cannot distinguish a looming object from a near and fast translatory moving object, because the latter can evoke a large amount of excitation that can lead to false LGMD1 spikes. This article presents a new visual neural system model (LGMD1) that applies a neural competition mechanism within a framework of separated ON and OFF pathways to shut off the translating response. The competition-based approach responds vigorously to monotonous ON/OFF responses resulting from a looming object. However, it does not respond to paired ON-OFF responses that result from a translating object, thereby enhancing collision selectivity. Moreover, a complementary denoising mechanism ensures reliable collision detection. To verify the effectiveness of the model, we have conducted systematic comparative experiments on synthetic and real datasets. The results show that our method exhibits more accurate discrimination between looming and translational events-the looming motion can be correctly detected. It also demonstrates that the proposed model is more robust than comparative models.

Optogenetic targeting of AII amacrine cells restores retinal computations performed by the inner retina

Most inherited retinal dystrophies display progressive photoreceptor cell degeneration leading to severe visual impairment. Optogenetic reactivation of inner retinal neurons is a promising avenue to restore vision in retinas having lost their photoreceptors. Expression of optogenetic proteins in surviving ganglion cells, the retinal output, allows them to take on the lost photoreceptive function. Nonetheless, this creates an exclusively ON retina by expression of depolarizing optogenetic proteins in all classes of ganglion cells, whereas a normal retina extracts several features from the visual scene, with different ganglion cells detecting light increase (ON) and light decrease (OFF). Refinement of this therapeutic strategy should thus aim at restoring these computations. Here we used a vector that targets gene expression to a specific interneuron of the retina called the AII amacrine cell. AII amacrine cells simultaneously activate the ON pathway and inhibit the OFF pathway. We show that the optogenetic stimulation of AII amacrine cells allows restoration of both ON and OFF responses in the retina, but also mediates other types of retinal processing such as sustained and transient responses. Targeting amacrine cells with optogenetics is thus a promising avenue to restore better retinal function and visual perception in patients suffering from retinal degeneration.

The direct influence of retinal degeneration on electrical stimulation efficacy: Significant implications for retinal prostheses.

Photoreceptor loss and inner retinal network remodeling severely impacts the ability of retinal prosthetic devices to create artificial vision. We developed a computational model of a degenerating retina based on rodent data and tested its response to retinal electrical stimulation. This model includes detailed network connectivity and diverse neural intrinsic properties, capable of exploring how the degenerated retina influences the performance of electrical stimulation during the degeneration process. Our model suggests the possibility of quantitatively modulating retinal ON and OFF pathways between phase II and III of retinal degeneration without requiring any differences between ON and OFF RGC intrinsic cellular properties. The model also provided insights about how remodeling events influence stage-dependent differential electrical responses of ON and OFF pathways.Clinical Relevance-This data-driven model can guide future development of retinal prostheses and stimulation strategies that may benefit patients at different stages of retinal disease progression, particularly in the early and mid-stages, thus increasing their global acceptance.

Impact of text contrast polarity on the retinal activity in myopes and emmetropes using modified pattern ERG

Environmental factors favoring myopia development are still being studied and there is accumulating evidence for a significant role of nearwork. Recently, reading standard black-on-white text was found to activate the retinal OFF pathway and induce choroidal thinning, which is associated with myopia onset. Contrarily, reading white-on-black text led to thicker choroids, being protective against myopia. Respective effects on retinal processing are yet unknown. Here, we exploratively assessed the impact of contrast polarity on the retinal activity and possible interactions with eccentricity and refractive error. We recorded pattern electroretinograms in myopic and emmetropic adults while presenting a dead leaves stimulus (DLS), overlaid by masks of different size in ring or circle shape, either filled with uniform gray or text of inverted or standard contrast. In myopes, retinal responses for DLS with standard and inverted contrast were larger when the perifovea was stimulated (6–12 deg), however, including the fovea resulted in smaller amplitudes for inverted contrast than in emmetropes. The retina of emmetropes was more sensitive to inverted contrast than to standard and gray within 12 deg, but most sensitive for gray in the perifovea. This demonstrates that the refractive error influences the sensitivity to text contrast polarity, with a special role of the peripheral retina, which is in line with previous studies about blur sensitivity. Defining whether the differences derive from retinal processing or anatomical features of a myopic eye requires further investigation. Our approach might be a first step to explain how nearwork promotes the eye’s elongation.

Functional organization of visual responses in the octopus optic lobe.

Cephalopods are highly visual animals with camera-type eyes, large brains, and a rich repertoire of visually guided behaviors. However, the cephalopod brain evolved independently from those of other highly visual species, such as vertebrates; therefore, the neural circuits that process sensory information are profoundly different. It is largely unknown how their powerful but unique visual system functions, as there have been no direct neural measurements of visual responses in the cephalopod brain. In this study, we used two-photon calcium imaging to record visually evoked responses in the primary visual processing center of the octopus central brain, the optic lobe, to determine how basic features of the visual scene are represented and organized. We found spatially localized receptive fields for light (ON) and dark (OFF) stimuli, which were retinotopically organized across the optic lobe, demonstrating a hallmark of visual system organization shared across many species. An examination of these responses revealed transformations of the visual representation across the layers of the optic lobe, including the emergence of the OFF pathway and increased size selectivity. We also identified asymmetries in the spatial processing of ON and OFF stimuli, which suggest unique circuit mechanisms for form processing that may have evolved to suit the specific demands of processing an underwater visual scene. This study provides insight into the neural processing and functional organization of the octopus visual system, highlighting both shared and unique aspects, and lays a foundation for future studies of the neural circuits that mediate visual processing and behavior in cephalopods.

Model-Based Approach Shows ON Pathway Afferents Elicit a Transient Decrease of V1 Responses.

Neurons in the primary visual cortex (V1) receive excitation and inhibition from distinct parallel pathways processing lightness (ON) and darkness (OFF). V1 neurons overall respond more strongly to dark than light stimuli, consistent with a preponderance of darker regions in natural images, as well as human psychophysics. However, it has been unclear whether this "dark-dominance" is because of more excitation from the OFF pathway or more inhibition from the ON pathway. To understand the mechanisms behind dark-dominance, we record electrophysiological responses of individual simple-type V1 neurons to natural image stimuli and then train biologically inspired convolutional neural networks to predict the neurons' responses. Analyzing a sample of 71 neurons (in anesthetized, paralyzed cats of either sex) has revealed their responses to be more driven by dark than light stimuli, consistent with previous investigations. We show that this asymmetry is predominantly because of slower inhibition to dark stimuli rather than to stronger excitation from the thalamocortical OFF pathway. Consistent with dark-dominant neurons having faster responses than light-dominant neurons, we find dark-dominance to solely occur in the early latencies of neurons' responses. Neurons that are strongly dark-dominated also tend to be less orientation-selective. This novel approach gives us new insight into the dark-dominance phenomenon and provides an avenue to address new questions about excitatory and inhibitory integration in cortical neurons.SIGNIFICANCE STATEMENT Neurons in the early visual cortex respond on average more strongly to dark than to light stimuli, but the mechanisms behind this bias have been unclear. Here we address this issue by combining single-unit electrophysiology with a novel machine learning model to analyze neurons' responses to natural image stimuli in primary visual cortex. Using these techniques, we find slower inhibition to light than to dark stimuli to be the leading mechanism behind stronger dark responses. This slower inhibition to light might help explain other empirical findings, such as why orientation selectivity is weaker at earlier response latencies. These results demonstrate how imbalances in excitation versus inhibition can give rise to response asymmetries in cortical neuron responses.

Morphological and sensorimotor phenotypes in a zebrafish CHARGE syndrome model are domain-dependent.

CHARGE syndrome is a heterogeneous disorder characterized by a spectrum of defects affecting multiple tissues and behavioral difficulties such as autism, attention-deficit/hyperactivity disorder, obsessive-compulsive disorder, anxiety, and sensory deficits. Most CHARGE cases arise from de novo, loss-of-function mutations in chromodomain-helicase-DNA-binding-protein-7 (CHD7). CHD7 is required for processes such as neuronal differentiation and neural crest cell migration, but how CHD7 affects neural circuit function to regulate behavior is unclear. To investigate the pathophysiology of behavioral symptoms in CHARGE, we established a mutant chd7 zebrafish line that recapitulates multiple CHARGE phenotypes including ear, cardiac, and craniofacial defects. Using a panel of behavioral assays, we found that chd7 mutants have specific auditory and visual behavior deficits that are independent of defects in sensory structures. Mauthner cell-dependent short-latency acoustic startle responses are normal in chd7 mutants, while Mauthner-independent long-latency responses are reduced. Responses to sudden decreases in light are also reduced in mutants, while responses to sudden increases in light are normal, suggesting that the retinal OFF pathway may be affected. Furthermore, by analyzing multiple chd7 alleles we observed that the penetrance of morphological and behavioral phenotypes is influenced by genetic background but that it also depends on the mutation location, with a chromodomain mutation causing the highest penetrance. This pattern is consistent with analysis of a CHARGE patient dataset in which symptom penetrance was highest in subjects with mutations in the CHD7 chromodomains. These results provide new insight into the heterogeneity of CHARGE and will inform future work to define CHD7-dependent neurobehavioral mechanisms.

Luminance Contrast Shifts Dominance Balance between ON and OFF Pathways in Human Vision.

Human vision processes light and dark stimuli in visual scenes with separate ON and OFF neuronal pathways. In nature, stimuli lighter or darker than their local surround have different spatial properties and contrast distributions (Ratliff et al., 2010; Cooper and Norcia, 2015; Rahimi-Nasrabadi et al., 2021). Similarly, in human vision, we show that luminance contrast affects the perception of lights and darks differently. At high contrast, human subjects of both sexes locate dark stimuli faster and more accurately than light stimuli, which is consistent with a visual system dominated by the OFF pathway. However, at low contrast, they locate light stimuli faster and more accurately than dark stimuli, which is consistent with a visual system dominated by the ON pathway. Luminance contrast was strongly correlated with multiple ON/OFF dominance ratios estimated from light/dark ratios of performance errors, missed targets, or reaction times (RTs). All correlations could be demonstrated at multiple eccentricities of the central visual field with an ON-OFF perimetry test implemented in a head-mounted visual display. We conclude that high-contrast stimuli are processed faster and more accurately by OFF pathways than ON pathways. However, the OFF dominance shifts toward ON dominance when stimulus contrast decreases, as expected from the higher-contrast sensitivity of ON cortical pathways (Kremkow et al., 2014; Rahimi-Nasrabadi et al., 2021). The results highlight the importance of contrast polarity in visual field measurements and predict a loss of low-contrast vision in humans with ON pathway deficits, as demonstrated in animal models (Sarnaik et al., 2014).SIGNIFICANCE STATEMENT ON and OFF retino-thalamo-cortical pathways respond differently to luminance contrast. In both animal models and humans, low contrasts drive stronger responses from ON pathways, whereas high contrasts drive stronger responses from OFF pathways. We demonstrate that these ON-OFF pathway differences have a correlate in human vision. At low contrast, humans locate light targets faster and more accurately than dark targets but, as contrast increases, dark targets become more visible than light targets. We also demonstrate that contrast is strongly correlated with multiple light/dark ratios of visual performance in central vision. These results provide a link between neuronal physiology and human vision while emphasizing the importance of stimulus polarity in measurements of visual fields and contrast sensitivity.

Efficient processing of natural scenes in visual cortex.

Neural circuits in the periphery of the visual, auditory, and olfactory systems are believed to use limited resources efficiently to represent sensory information by adapting to the statistical structure of the natural environment. This "efficient coding" principle has been used to explain many aspects of early visual circuits including the distribution of photoreceptors, the mosaic geometry and center-surround structure of retinal receptive fields, the excess OFF pathways relative to ON pathways, saccade statistics, and the structure of simple cell receptive fields in V1. We know less about the extent to which such adaptations may occur in deeper areas of cortex beyond V1. We thus review recent developments showing that the perception of visual textures, which depends on processing in V2 and beyond in mammals, is adapted in rats and humans to the multi-point statistics of luminance in natural scenes. These results suggest that central circuits in the visual brain are adapted for seeing key aspects of natural scenes. We conclude by discussing how adaptation to natural temporal statistics may aid in learning and representing visual objects, and propose two challenges for the future: (1) explaining the distribution of shape sensitivity in the ventral visual stream from the statistics of object shape in natural images, and (2) explaining cell types of the vertebrate retina in terms of feature detectors that are adapted to the spatio-temporal structures of natural stimuli. We also discuss how new methods based on machine learning may complement the normative, principles-based approach to theoretical neuroscience.

Contrast polarity and myopia

AbstractTo transmit the visual information detected by 125 Million photoreceptors in the retina through the optic nerve, with only about 1 Million ganglion cell axons, the retina has to compress information down to about 1 percent. Aside of receptor pooling, a major trick is to form receptive fields with ON/OFF structure which compare brightness in the center with the brightness in the periphery and reduce the information to spatial–temporal differences, while absolute luminances largely ignored. Two major types are found: ON center, which are activated by light in the center and inhibited by light in the periphery and OFF center with the inverse response patterns. Such receptive fields are perfectly suited to detect defocus which represents low pass filtering of the spatial frequencies in the image. It was found in animal models that suppression of ON pathways is generally related to more axial eye growth and can enhance deprivation myopia while suppression of OFF has little or an inverted effect. Analysing the ON and OFF input strength in our visual environment, we found that reading text with conventional contrast overstimulates OFF channels while reading with inverted contrast strongly stimulates ON channels. After reading for one hour, we found that the choroid becomes thinner with conventional text, but thicker with contrast‐inverted text. Since there is considerable published evidence that choroidal thickening is a precursor of myopia inhibition, reading text with inverted contrast may be beneficial against myopia progression. We have also tested different text sizes. The effect was not observed with a letter height of 0.25 deg (like on a smart phone) but prominent at 0.5 deg (like in a book). Interestingly, choroidal thickening was induced both in emmetropic and myopic subjects, suggesting that the approach should also work in myopes. We have previously found that myopic subjects show a reduced choroidal response, compared to emmetropes, when positive defocus was imposed for 30 min. The functional deficit in the myopic retina appears limited to the detection of defocus while the activity of ON and OFF pathways is not affected. A major question for future research is whether and how ON/OFF processing may be linked to the detection of the sign of defocus by the retina.Research supported by IOB.No proprietary interest.

Insights into myopia gleaned from retinal electrophysiology

AbstractThe prevalence of myopia is increasing dramatically. Retinal signalling controls eye growth and a retinal myopia‐signalling cascade has been postulated. One of the strongest genetic associations with myopia susceptibility is a locus near the GJD2 gene which codes for a protein forming gap junctions in the retina. We explored whether any parameters of retinal electrophysiology were associated with presence of the risk allele. Full‐field scotopic and photopic electroretinogram (ERG) recording was performed in over 200 healthy volunteers from the TwinsUK cohort. Responses were elicited by stimuli conforming to international standard protocols and additional experimental protocols aimed at isolating rod and cone system responses. The majority of participants had been genotyped previously for their identity at the relevant locus. A mixed linear model was employed with ERG parameters (amplitudes and peak times) as outcomes and allelic dosage at the relevant locus as a predictor, adjusting for age, sex and inter‐individual relatedness. ERG recordings and genotype data were available for the majority of participants (95% female; mean (SD) age 64.2 (9.7) years). Light adapted single‐flash a‐waves and b‐waves associated significantly with allelic identity at the locus of interest. None of the standard dark‐adapted ERG parameters associated significantly with genotype at this locus. Further investigation of responses to experimental protocols, and those obtained from patients with loss of ON or both ON and OFF bipolar cell responses, suggested changes specific to the cone‐driven OFF pathway. The findings suggest associations between photopic cone‐driven retinal electrophysiological signalling and one of the genetic polymorphisms most strongly linked to myopia. Higher environmental light levels are known to be protective in myopia, and our results support the hypothesis that changes in light‐adapted cone system signalling might play a role in myopia development.

Comparing the RETeval® portable ERG device with more traditional tabletop ERG systems in normal subjects and selected retinopathies

PurposeOur study aimed to determine if ISCEV standard-like ERGs recorded with the LKC RETeval® portable ERG unit compared to those obtained using the more traditional tabletop unit.MethodsERGs recorded from normal subjects and patients affected with retinal ON and OFF pathway anomalies were compared. Analysis included peak time and amplitude measurements as well as time–frequency domain analysis with the discrete wavelet transform of waveforms obtained with the two systems.ResultsAlthough both systems were similarly able to record reliable and highly reproducible ERG responses, there were major discrepancies in ERG responses between the portable and tabletop units, pointing toward a weaker stimulation of the retinal OFF pathway with the portable RETeval® unit.ConclusionThe portable RETeval® unit appears to be able to record highly reproducible and diagnostically useful clinical ERGs, albeit with some significant differences in waveform composition compared to those obtained with more standard tabletop systems. Given the unknown origin of these waveform discrepancies, if left uncorrected, these differences could potentially lead to erroneous interpretation when used in the clinical context and/or compared to ERGs recorded using more traditional table top units. Clearly, more research is warranted before handheld devices, such as the RETeval®, can be homologated as a diagnostically sound ERG devices.

Cortical mechanisms of visual brightness.

SUMMARYThe primary visual cortex signals the onset of light and dark stimuli with ON and OFF cortical pathways. Here, we demonstrate that both pathways generate similar response increments to large homogeneous surfaces and their response average increases with surface brightness. We show that, in cat visual cortex, response dominance from ON or OFF pathways is bimodally distributed when stimuli are smaller than one receptive field center but unimodally distributed when they are larger. Moreover, whereas small bright stimuli drive opposite responses from ON and OFF pathways (increased versus suppressed activity), large bright surfaces drive similar response increments. We show that this size-brightness relation emerges because strong illumination increases the size of light surfaces in nature and both ON and OFF cortical neurons receive input from ON thalamic pathways. We conclude that visual scenes are perceived as brighter when the average response increments from ON and OFF cortical pathways become stronger.